Journal of Clinical Endocrinology & Metabolism, Vol 78, 440-448, Copyright © 1994 by Endocrine Society

ARTICLES

RU 486 action after estrogen priming in the endometrium and oviducts of rhesus monkeys (Macaca mulatta)

OD Slayden and RM Brenner
Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006.

Recently, we reported that in rhesus monkeys, RU 486 treatment could inhibit the ability of estradiol (E2) to stimulate endometrial regeneration without inhibiting E2-dependent oviductal regeneration. In that work, RU 486 had been administered at the end of an artificial luteal phase when the oviducts were regressed, the endometrium was in a late secretory state, and estrogen and progestin receptors (ER and PR, respectively) were at minimal levels in both organs. In the current work, we administered RU 486 after 2 weeks of estrogen priming when the oviducts were fully differentiated, the endometrium was in a proliferative state, and ER and PR levels were maximal. Our goal was to determine whether the degree to which RU 486 inhibited E2 action in either organ varied depending on their initial state. Spayed rhesus monkeys were primed with E2 for 2 weeks and then treated in four different ways for an additional 2 weeks as follows: I) E2; II) E2 plus P; III) E2, P, and RU 486; and IV) E2 plus RU 486. Menstruation was not induced by any of the four treatments. In group I, continuous treatment with E2 maintained a typical proliferative endometrium with abundant Ki- 67-positive cells, low levels of apoptosis, and elevated ER and PR; the oviducts were also maintained in a fully ciliated-secretory state. In group II, P induced a typical progestational secretory state in the endometrium, with few proliferating (Ki-67-positive) epithelial cells, undetectable apoptosis, and decreased ER and PR; as expected, the oviducts were fully regressed, with few Ki-67-positive or ciliated epithelial cells and low levels of ER and PR. In the endometria of monkeys treated with RU 486 and E2, either with (group III) or without (group IV) P, the effects of E2 on wet weight, thickness, and epithelial proliferation were more dramatically inhibited than in our previous study. However, the oviducts of the RU 486-treated animals had remained in a hypertrophied, fully ciliated-secretory state as in our previous study, with elevated ER and nuclear PR, although epithelial proliferation was suppressed. The degree to which RU 486 can inhibit estrogen-dependent growth in the endometrium can apparently be affected by the state of differentiation and/or steroid receptor level at the time the antiprogestin treatment is begun, but this effect is not evident in the oviduct, which shows only modest antiproliferative effects of the RU 486 treatment.

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